International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

How Tongxie-Yaofang Regulates Intestinal Synaptic Plasticity by Activating Enteric Glial Cells and NGF/TrkA Pathway in Diarrhea-Predominant Irritable Bowel Syndrome Rats.

Purpose: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a frequent functional gastrointestinal disease that affects health and quality of life owing to its high incidence and recurrence rate. Tongxie-Yaofang (TXYF) is a traditional Chinese medicine prescribed for D-IBS. However, the therapeutic mechanism of TXYF has not been fully elucidated. This study aimed to investigate the effects of TXYF on visceral hypersensitivity in stress-induced D-IBS rats and the underlying mechanisms. Methods: Electromyographic (EMG) activity of the external oblique muscles and the abdominal withdrawal reflex (AWR) score captured by Barostat were used to quantify the effect of TXYF on visceral sensitivity. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the enteric nervous system (ENS). For molecular detection, the colonic expression of enteric glial cell's (EGC's) activation markers, glial fibrillary acidic protein (GFAP) and calcium-binding protein S100ß, NGF, TrkA, synaptic plasticity-related factors, synaptophysin (SYN) and postsynaptic density-95 (PSD-95), glutamate, glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), and N-methyl-D-aspartate receptor (NMDAR) were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time PCR. An ex vivo experiment was conducted to measure the EGC-induced NGF release. Results: TXYF decreased the EMG activity and AWR scores in rats with D-IBS. Under TEM, TXYF improved the dense and irregular nerve arrangement, narrowed the synaptic cleft, and decreased the number of synaptic vesicles in D-IBS rats. In addition, TXYF decreased the expression of GFAP, S100ß, SYN, and PSD-95; down-regulated the levels of NGF, TrkA, and glutamate; and reduced the mRNA expression of AMPAR1, NMDAR1, and NMDAR2B. In an ex vivo experiment, TXYF decreased NGF release in D-IBS rats, and this trend disappeared under EGC inhibition. Conclusion: TXYF alleviated visceral hypersensitivity in D-IBS rats possibly by improving synaptic plasticity through inhibiting the activity of EGCs and the NGF/TrkA signaling pathway in the colon.

Identification of the therapeutic effect and molecular mechanism of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) theory believes that clearing heat and promoting dampness is the main treatment method for chronic gastritis. Coptis chinensis Franch. has the effects of clearing heat, detoxifying, and anti-inflammatory; Magnolia officinalis var. biloba can be used to treat abdominal pain, cough, and asthma. Coptis chinensis Franch. and Magnolia officinalis var. biloba can regulate the balance of intestinal microbiota and inhibit inflammatory reactions. AIM: This study will verify the therapeutic effect of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis, and explore its mechanism through transcriptome sequencing. METHODS: Firstly, a rat chronic gastritis model was established, and the anal temperature and body weight changes of the rats before and after modeling were observed. Next, H&E staining, TUNEL assay and ELISA assay were performed on rat gastric mucosal tissues. Subsequently, the key fractions of Coptis chinensis Franch. and Magnolia officinalis var. biloba were obtained by high performance liquid chromatography (HPLC), and a GES-1 cell inflammation model was constructed to select the optimal monomer. Finally, the mechanism of action of Coptis chinensis Franch. and Magnolia officinalis var. biloba was explored through RNA seq. RESULTS: Compared with the control group, the rats in the administered group were in better condition, with higher anal temperature, reduced inflammatory response in gastric mucosal tissue and reduced apoptosis. The optimal fraction Coptisine was subsequently determined by HPLC and GES-1 cell model. RNA-seq analysis revealed that DEG was significantly enriched in ribosomes, NF-κB signaling pathway, etc. The key genes TPT1 and RPL37 were subsequently obtained. CONCLUSIONS: This study verified the therapeutic effects of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis by in vivo and in vitro experiments in rats, identified Coptisine as the optimal component, and obtained two potential target genes.

Different therapies of Chinese herbal medicine for diarrhea-predominant irritable bowel syndrome: A network meta-analysis of double-blinded, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuganjianpi Therapy (SGJP), Jianpi Therapy (JP), Shugan Therapy (SG), Jianpiwenshen Therapy (JPWS), and Shuganjianpiwenshen Therapy (SGJPWS), consisting of formulas from Chinese herbal medicine (CHM), have been tremendously applied to irritable bowel syndrome (IBS). However, it remains uncertain when exploring the preferable option among different CHM therapies for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM OF THE STUDY: To compare and rank the efficacy and safety of different CHM therapies for IBS-D. MATERIALS AND METHODS: We searched randomized, double-blinded, placebo-controlled trials through mainstream databases from their inception to October 31, 2022. Eligible randomized controlled trials (RCTs) applied one of the CHM therapies as the experimental group and placebo as the control group. Two authors independently extracted data into a form and evaluated the quality of the retrieved articles by the Cochrane Risk of Bias Tool. At least one of the following outcomes was assessed: Serotonin, Neuropeptide Y (NPY), Incidence of Adverse Events (AE), and Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) with its subscales of Severity of Abdominal Pain (SAP), Frequency of Abdominal Pain (FAP), Severity of Abdominal Distension (SAD), Dissatisfaction with Bowel Habits (DBH), and Interference with Quality of Life (IQOL). A Bayesian network meta-analysis on a random-effect model was conducted using R 4.2.2 software. RESULTS: 1367 records were retrieved from databases in an initial search. Fourteen studies involving six interventions with 2248 participants were identified. Provided pairwise comparisons, the surface under the cumulative ranking curve (SUCRA) ranking, and cluster analysis, JPWS was the best option for ameliorating clinical symptoms simultaneously, which included IBS-SSS, SAP, FAP, SAD, DBH, and IQOL. As for AE, JPWS contributed to fewer adverse events than others as well. In respect of serum indicators, we noticed the dominance of SGJP in regulating both serotonin and NPY. CONCLUSIONS: JPWS and SGJP were the most prominent CHM therapies for IBS-D in terms of clinical symptoms, including abdominal pain, distension, bowel habits, and improvement of quality of life. The effect of JP and SG for IBS-D required further investigation. As a potential candidate, SGJP may well treat IBS-D by mediating dysmotility, visceral hypersensitivity, and the gut-brain axis with an increase of NPY and a reduction of serotonin. For safety, JPWS was ideal for the fewest adverse events in the treatment of IBS-D. On account of a small sample size and possible geographical publication bias, more double-blinded and placebo-controlled trials with larger samples worldwide would be necessary for strengthening current evidence.

The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated. AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments. MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model. RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of ß-catenin, accelerating the cell cycle and promoting cell proliferation in vitro. CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/ß-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.

A Network Pharmacology-Based Study on Irritable Bowel Syndrome Prevention and Treatment Utilizing Shenling Baizhu Powder.

METHODS: Metabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound's structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the "compound-traditional Chinese medicine/molecule-target-pathway" network. Molecular docking was used to verify the core protein and its related small molecular compounds. RESULT: There were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate-5-lipoxygenase (ALOX5), B-cell lymphoma-2 (BCL2), recombinant cyclin D1 (CCND1), and catenin-ß1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3',4'-heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7-O-glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway. CONCLUSION: This study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.

Role of gut microbiota in functional constipation.

Functional constipation (FC) is common, yet the etiology is not clear. Accumulating evidence suggests an association between FC and abnormal gut microbiota. The relationship between the gut microbiota and the gut transit is likely bidirectional. This review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of FC. By modulating the colonic motility, secretion, and absorption, gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids, short-chain fatty acids, 5-hydroxytryptamine, and methane. In support of the key roles of the gut microbiota in FC, treatment with probiotics, prebiotics, synbiotics, and traditional Chinese medicine often result in compositional and functional changes in the gut microbiota. Further studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.

Systematic review and pathway enrichment analysis of Chinese medicine in preventing recurrence and improving prognosis of cholelithiasis after gallbladder-preserving lithotripsy.

BACKGROUND: Traditional Chinese medicine (TCM) may improve the prognosis management of cholelithiasis patients after gallbladder-preserving lithotripsy. To explore the evidence for this view, we systematically reviewed the efficacy and safety of TCM for improving the prognosis of cholelithiasis after gallbladder-preserving lithotripsy and performed functional pathway enrichment analysis of TCM target genes. METHODS: In this systematic review (SRs), we searched six Chinese or international databases to collect randomized controlled clinical trials (RCTs) of TCM in preventing the recurrence of cholelithiasis after gallbladder-preserving lithotripsy. The literature was independently screened by 2 reviewers, who then extracted the data. The Cochrane risk-of-bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used to assess the included studies' risk of bias and quality of evidence, respectively. And, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses would be conducted on the TCM prescriptions in the included literature to find the effective component and mechanism of TCM in the prognosis management of gallbladder-preserving lithotripsy. Analysis in this research would be conducted by R 3.5.2 software. RESULTS: A total of 1,024 articles were retrieved, and 9 RCTs involving 926 participants were included after the step-by-step screening. The risk of bias for each important outcome in all the studies was "uncertain". The meta-analysis showed that compared with blank control, TCM prevented cholelithiasis by decreasing the recurrence rate, complications incidence, gallbladder wall thickness, and gallbladder contraction degree. But, there were no significant differences in the rate of the adverse reaction. The result of the GO and KEGG analysis revealed that the mechanism of prevention of TCM in gallstone recurrence may be related to the cholesterol metabolic pathway and that naringin from Glycyrrhiza may be the effective component in the prevention of recurrence. CONCLUSIONS: Existing evidence suggests that the use of TCM may reduce the recurrence rate after gallbladder-preserving lithotripsy and this effect may be related to the flavonoid glycoside naringin from Glycyrrhiza uralensis, but more RCTs with high quality in this area may be needed to have a robust conclusion.

Modified Xiaochaihu Decoction for gastroesophageal reflux disease: A randomized double-simulation controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the symptoms of GERD, but the effects of MXD on GERD manifestations and relapse prevention need to be further explained. Therefore, we performed a prospective, double-blind, and double-simulation study. AIM: To verify the efficacy of MXD for GERD and its effect on esophageal motility. METHODS: Using randomization, double-blinding, and a simulation design, 288 participants with GERD were randomized to the treatment group and control group and received herbs (MXD) plus omeprazole simulation and omeprazole plus herbs simulation, respectively, for 4 wk. The GERD-Q scale score and esophageal manometry were measured at baseline, after treatment, and at 1 mo and 3 mo follow-up visits when medication was complete to evaluate recurrence indicators. RESULTS: The GERD-Q scale score in both groups decreased significantly compared to those before treatment (P < 0.01). However, no significant difference was observed between the two groups (P > 0.05). Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing (more than 50%) improved in both groups from baseline (P < 0.01), especially in the treatment group (P < 0.05). The percentage of small intermittent contractions, large intermittent contractions, and increased pre-phase contractions in the treatment group significantly improved compared with baseline (P < 0.05) but did not improve in the control group (P > 0.05). There was no significant difference between the groups after treatment (P > 0.05). The percentage of weak esophageal contractility (distal contractile integral < 450 mmHg·s·cm), improved in both groups (P < 0.01), but no significant difference was observed between the groups after treatment (P > 0.05). The relapse rate in the treatment group was lower than that in the control group at the 1 mo (P < 0.01) and 3 mo follow-up (P < 0.05). CONCLUSION: MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD. The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.

Development of a novel green tea quality roadmap and the complex sensory-associated characteristics exploration using rapid near-infrared spectroscopy technology.

Nondestructive instrumental identification of the green tea quality instead of professional human panel tests is highly desired for industrial application recently. The special flavor is a key quality-trait that influence consumer preference. However, flavonoids, as well as sensory-associated compounds, which play a critical role in the quality-traits profile of green tea samples have been poorly investigated. In this study, we were proposing an objective and accurate near infrared spectroscopy (NIRS) profile to support quality control within the entire green tea sensory evaluation chain, the complexity of green tea samples' sensory analysis was performed by two complementary methods: the standard calculation and the novel NIRS roadmap coupled with chemometrics. The green tea samples' physical quality, gustatory index, and nutritional index were measured respectively, which taking into consideration the gustatory evaluation of green tea for five commercially representative overall quality ("very bad", "bad", "regular", "good" and "excellent"). Our findings highlight the underexplored role of NIRS in chemical-to-sensory relationships and its widespread importance and utility in green tea quality improvement. Collectively, the comprehensive characterization of sensory-associated attribution allowed the identification of a wide array of spectrometric features, mostly related to moisture, soluble solids (SS), tea polyphenol (TPP), epigallocatechin gallate (EGCG), epicatechin (EC) and tea polysaccharide (TPS), which can be used as putative biomarkers to rapidly evaluate the green tea flavor variations related to rank differences. Otherwise, the NIRS' data were split into the calibration (n = 80) and prediction (n = 40) set independently, which showed high correlation coefficient with Rp-values of 0.9024, 0.9020 in physical and total cup quality, respectively. In this research, we demonstrated that NIRS was an easily-generated strategy and able to close the loop to feedback into the process for advanced process control. However, the established models should be improved by more green tea samples from different regions.

Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis.

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.

Bu-Zhong-Yi-Qi Granule Enhances Colonic Tight Junction Integrity via TLR4/NF-κB/MLCK Signaling Pathway in Ulcerative Colitis Rats.

BACKGROUND: Bu-zhong-yi-qi granule (BZYQ), a sort of Chinese herbal medicine, has exhibited therapeutic effects on ulcerative colitis (UC). However, the mechanism of BZYQ has not been fully clarified. This study was aimed at investigating the effects of BZYQ on UC rats model and at exploring its potential mechanism. METHODS: The UC rats were established by enema of trinitrobenzene sulfonic acid (TNBS). The therapeutic effects of BZYQ treatment were evaluated by disease activity index (DAI), colon macroscopic damage index (CMDI) scores, and histological observation. The mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-10 (IL-10) were measured by quantitative real time-polymerase chain reaction (qPCR). The expression of tight junction (TJ) proteins, occludin and claudin-1, in the colon was determined by Western blot and immunofluorescence. The expression of toll-like receptors 4 (TLR4), nuclear factor-kappa B (NF-κB), p-NF-κB, myosin light chain kinase (MLCK), MLC, and p-MLC levels in colon was determined by Western blot or qPCR. RESULTS: The results showed that BZYQ could attenuate DAI, CMDI, and histological inflammation. TJ proteins expression was decreased in UC rats, but treatment with BZYQ restored the expression of occludin and claudin-1. In addition, BZYQ administration ameliorated UC-associated increase in the production of TNF-α, IL-1ß, and the expression of TLR4, NF-κB, p-NF-κB, MLCK, MLC, and p-MLC, while BZYQ administration increased the production of IL-10. CONCLUSIONS: The therapeutic effect of BZYQ on UC is at least partially through regulation of the secretion of some inflammatory cytokines and improvement of TJ integrity via TLR4/NF-κB/MLCK pathway.

Qingre Jianpi decoction attenuates inflammatory responses by suppressing NOD-like receptor family pyrin domain-containing 3 inflammasome activation in dextran sulfate sodium-induced colitis mice.

OBJECTIVE: To investigate the effects of Qingre Jianpi decoction (，QRJPD) on dextran sulfate sodium (DSS)-induced colitis mice and explore its mechanism. METHODS: All mice were randomly divided into six groups. Weight changes, disease activity index values, and histological damage were detected. Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC) method. The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were detected by western blot analysis, IHC, and quantitative reverse transcription polymerase chain reaction. RESULTS: QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis (UC), reduced the secretion of inflammatory cytokines, and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome. CONCLUSION: QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.

Efficacy of Shenlingbaizhu formula on irritable bowel syndrome: a systematic review.

OBJECTIVE: To evaluate the effectiveness and safety of a Shenlingbaizhu (SLBZ) formula in the treatment of irritable bowel syndrome (IBS). The effectiveness of SLBZ with or without conventional treatment was compared to that of conventional treatment alone. METHODS: A comprehensive literature search of four Chinese electronic databases, three English language databases, and two English language trial registries from inception to June 2019 was performed. Two authors independently screened the citations and retrieved full publications of randomized trials on the use of SLBZ with or without conventional treatment for IBS. The methodological quality of the trials was assessed with the Cochrane Collaboration's tool for assessing the risk of bias. Data were extracted and subjected to Meta-analysis to compare the efficacy of the SLBZ formula with or without conventional treatment to conventional treatment alone. RESULTS: Thirteen trials (comprising a total of 868 patients with IBS) were included in this review. The risk of bias of all 13 included trials was assessed as moderate. The SLBZ formula was associated with significant improvements in cure rate [relative risk (RR) score of 2.38, 95% confidence interval (CI) 1.43 to 3.95, I 2 = 0%; 8 trials, n = 487, fixed-effects model (FEM)], diarrhea severity score [mean difference (MD) score of －0.62, 95% CI －1.05 to －0.20, I 2 = 88%; 4 trials, n = 286, random effects model (REM)], abdominal pain severity score (MD score of －0.61, 95% CI －0.70 to －0.52, I 2 = 63%; 4 trials, n = 286, FEM), and abdominal distention severity score (MD score of －0.88, 95% CI －1.54 to －0.21, I 2 = 91%; 3 trials, n = 226, REM) compared to the conventional treatment alone. Adverse events were reported in five trials but only one of these indicated any adverse events associated with SLBZ. CONCLUSION: Based on the 13 trials reviewed here, the SLBZ formula with or without conventional treatment appeared to be safe and more effective in improving the cure rate and reducing the severity of diarrhea, abdominal pain, and abdominal distention compared to conventional treatment alone. However, these trials only generated a moderate quality of evidence, and well-designed and high-quality random controlled trials of the SLBZ formula for the treatment of IBS are required to confirm the efficacy of this treatment option.

Near-Infrared Spectroscopy as a Process Analytical Technology Tool for Monitoring the Steaming Process of Gastrodiae rhizoma with Multiparameters and Chemometrics.

Steaming is a vital unit operation in traditional Chinese medicine (TCM), which greatly affects the active ingredients and the pharmacological efficacy of the products. Near-infrared (NIR) spectroscopy has already been widely used as a strong process analytical technology (PAT) tool. In this study, the potential usage of NIR spectroscopy to monitor the steaming process of Gastrodiae rhizoma was explored. About 10 lab scale batches were employed to construct quantitative models to determine four chemical ingredients and moisture change during the steaming process. Gastrodin, p-hydroxybenzyl alcohol, parishin B, and parishin A were modeled by different multivariate calibration models (SMLR and PLS), while the content of the moisture was modeled by principal component regression (PCR). In the optimized models, the root mean square errors of prediction (RMSEP) for gastrodin, p-hydroxybenzyl alcohol, parishin B, parishin A, and moisture were 0.0181, 0.0143, 0.0132, 0.0244, and 2.15, respectively, and correlation coefficients (R p 2) were 0.9591, 0.9307, 0.9309, 0.9277, and 0.9201, respectively. Three other batches' results revealed that the accuracy of the model was acceptable and that was specific for next drying step. In addition, the results demonstrated the method was reliable in process performance and robustness. This method holds a great promise to replace current subjective color judgment and time-consuming HPLC or UV/Vis methods and is suitable for rapid online monitoring and quality control in the TCM industrial steaming process.

Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia.

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

Modified Liu-Jun-Zi decoction alleviates visceral hypersensitivity in functional dyspepsia by regulating EC cell-5HT3r signaling in duodenum.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Liu-Jun-Zi (MLJZ) is derived from one of the most famous traditional Chinese prescription Liu-Jun-Zi. It exhibits therapeutic effects in functional dyspepsia (FD), but the underlying mechanisms remain not well understood. Enterochromaffin (EC) cells contribute to the pathogeneses of visceral hypersensitivity in functional gastrointestinal disorders. But whether and how EC cells in duodenum participate in the mechanism of FD remain unsettled. AIM OF THE STUDY: To detect the crucial factors related to EC cells, and to evaluate the therapeutic effect of MLJZ and to determine whether MLJZ relieves visceral hypersensitivity in FD by regulating EC cell-5-hydroxytryptamine 3 receptor (5HT3r) signaling. MATERIALS AND METHODS: FD rats were established by iodoacetamide gavage combined with tail clamping method. The verification of FD model and the evaluation of the therapeutic effect of MLJZ was taken place by hematoxylin-eosin (HE) staining and visceral sensitivity measurement. The expression of EC cells and 5-hydroxytryptamine (5HT) in duodenum was detected by Immunohistochemistry (IHC) staining and enzyme-linked immunosorbent assay (ELISA). IHC staining and quantitative polymerase chain reaction (qPCR) were applied to measure the expression of tryptophan hydroxylase-1 (TPH1), paired box gene 4 (PAX4), transient receptor potential A1 (TRPA1), transient receptor potential C4 (TRPC4) and 5HT3r. Duodenum sections were stained by double immunofluorescence (IF) to study the synthesis of 5HT in EC cells. RESULTS: The gastric sensitivity increased in FD rats while MLJZ decoction significantly attenuated visceral hypersensitivity. The duodenum of FD rats displayed increased expressions of EC cells, 5HT, TPH1, PAX4 and 5HT3r. And the overexpression was reduced in response to MLJZ decoction treatment. CONCLUSIONS: EC cell-5HT3r signaling pathway is abnormally active in FD with visceral hypersensitivity. And MLJZ decoction can alleviates visceral hypersensitivity in FD by regulating EC cell-5HT3r signaling in duodenum.

Sini San ameliorates duodenal mucosal barrier injury and low­grade inflammation via the CRF pathway in a rat model of functional dyspepsia.

The gut­brain interaction is associated with impaired duodenal mucosal integrity and low­grade inflammation, which have been proven to be important pathological mechanisms of functional dyspepsia (FD). Sini San (SNS) is a classical Chinese medicine used to treat FD, but its underlying mechanisms are poorly understood. The aim of the present study was to evaluate the effects of SNS on duodenal mucosal barrier injury and low­grade inflammation with FD, and to assess its potential molecular mechanisms on the brain­gut axis. FD rats were established using the iodoacetamide and tail­squeezed methods. The expression of corticotropin­releasing factor (CRF), CRF receptor 1 (CRF­R1) and CRF­R2, were determined by western blot analysis and/or immunohistochemistry (IHC). In addition, mast cell (MC) migration was assessed by IHC with an anti­tryptase antibody, and histamine concentration was quantified using ELISA. The mRNA expression levels of tryptase and protease­activated receptor 2 (PAR­2) were quantified using reverse transcription­quantitative PCR, and the protein expression levels of zona occludens protein 1 (ZO­1), junctional adhesion molecule 1 (JAM­1), ß­catenin and E­cadherin were determined via western blot analysis. It was demonstrated that the expression level of CRF was downregulated in the central nervous system and duodenum following SNS treatment, and that SNS modulated the expression of both CRF­R1 and CRF­R2. In addition, SNS suppressed MC infiltration and the activity of the tryptase/PAR­2 pathway in the duodenum. Furthermore, treatment with SNS restored the normal expression levels of ZO­1, JAM­1 and ß­catenin in FD rats. These findings suggested that the therapeutic effects of SNS on FD were achieved by restoring mucosal barrier integrity and suppressing low­grade inflammation in the duodenum, which was at least partially mediated via the CRF signaling pathway.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Effects of Fengliao-Changweikang in Diarrhea-predominant Irritable Bowel Syndrome Rats and Its Mechanism Involving Colonic Motility.

BACKGROUND/AIMS: This study was designed to investigate the effect of Fengliao-Changweikang (FLCWK) in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its underlying mechanisms. METHODS: IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). In in vivo experiments, the model rats were randomly divided into 5 groups: NMS + RS, FLCWK (low dose, middle dose, and high dose), and pinaverium bromide. The normal control (no handling) rats were classified as the NH group. The therapeutic effect of FLCWK was evaluated by fecal characteristics, electromyographic response and abdominal withdrawal reflex scores. In in vitro experiments, the model rats were randomly divided into 2 groups: NMS + RS, FLCWK (middle dose), and no handling rats were used as the NH group. The differences in basic tension and ACh-induced tension of isolated colonic longitudinal smooth muscle strips (CLSMs) among the 3 groups were observed. In addition, different inhibitors (nifedipine, TMB-8, L-NAME, methylene blue, and 4-AP) were pretreated to explore the underlying mechanisms. RESULTS: In in vivo experiments, fecal characteristics, electromyographic response, and abdominal withdrawal reflex scores significantly improved in the FLCWK group, compared with the NMS + RS group. In in vitro experiments, the basic tension and ACh-induced tension of CLSMs in IBS-D rats were significantly inhibited by FLCWK. After pre-treatment with different inhibitors, the ACh-induced tension of CLSMs in each group showed no significant difference. CONCLUSIONS: FLCWK manifested curative effect in IBS-D rats by inhibiting colonic contraction. The underlying mechanisms may be related to regulatory pathway of nitric oxide/cGMP/Ca²âº and specific potassium channels.